Cocaine addiction continues to be a major public health issue in the United States today. Over time a population of hard core addicts has developed that appear refractory to treatment. In part the development of effective therapies has bene hindered by a lack of understanding of the changes in the response to cocaine with repeated exposure, as well as the residual changes in brain function and structure that can persist despite prolonged periods of abstinence from drug use. The development of non-invasive imaging methods in recent years has made it possible to investigate the neurobiological sequella of cocaine addiction and abstinence directly in humans and relate neurobiological changes to the clinical changes that occur over the course of abstinence. The purpose of experiments proposed in the present application is to investigate the nature and characteristics of the residual changes that persist during abstinence from extended abuse of cocaine using positron emission tomography. In the proposed experiments abstinent cocaine addicts in treatment will be compared to normal controls and current cocaine users in a cross sectional comparison of changes in functional activity as reflected in changes in rates of glucose utilization measured with [18F]fluorodeoxyglucose. A second goal is to determine if the pattern of functional activity seen in abstainers changes with continued abstinence from cocaine. Glucose landscapes obtained early in treatment will be compared to those obtained later in abstinence after sustained treatment. We will compare differences in the abstainers to differences in the scans obtained in normals and users as controls. Although the acute effects of cocaine are relatively brief, persistent alterations in neural function that far outlast the presence of cocaine at its binding sites are also engendered. Recovery from these changes is not likely to be a unitary phenomenon occurring at the same rate in all brain regions. The final goal is to determine if the patterns of functional activity obtained from abstainers following longer periods of abstinence are more like those of normals or cocaine users. It is hoped that this approach will provide important insights into the process of abstinence and provide a basis for developing both pharmacological and behavioral therapies that aid in maintaining abstinence from cocaine.